JP2009528532A - Incubator apparatus and method - Google Patents

Abstract

The present invention relates to a method of processing analysis using a portable incubator apparatus. The incubator apparatus 10 includes a plurality of cavities 20 configured to contain the analyte to be incubated. The method includes: placing the analyte in individual cavities; incubating the analyte in the cavities, wherein the incubator device enters the cavities separately from each other The incubator device is moved from the first position to the second position while the analyte is incubated, and if the incubator device is moving, the power supply and incubator device Independent of the external device, it is configured to maintain desirable conditions.

Description

(Field of Invention)
The present invention relates to a method of processing an analyte using a portable incubator device and such a portable incubator device.

(Background of the Invention)
In biological and chemical assays such as protein crystallization, variables such as buffer composition, concentration, pH, and type of chemical additive often need to be screened and controlled. In recent years, the test method has been performed by the parallel method. For example, the assay is automated and performed on a two-dimensional array of analyte samples so that data can be obtained simultaneously from the analyte samples in that array. This in turn reduces the time and cost involved in such an assay.

  In protein crystallization, the crystallization conditions for a given protein can be optimized by examining a parameter space that depends on temperature, pH, ionic strength and added drug. Common considerations include dispensing the crystallization solution into a container, sealing the container, and incubating the solution placed in the container, typically for a week to three months. The solution placed in the container during this period is examined for crystal formation, for example under a microscope. Obviously, such studies are exhaustive and the procedure is therefore iterative and may take a lot of time. Therefore, the time and cost involved can be reduced by conducting a parallel method.

  Many incubators with temperature control capability have been reported. Such incubators can be used for protein crystallization studies. In one example, the incubator has an aluminum plate, such as a microtiter plate that defines an array of wells configured to contain proteins in solution. In use, hot and / or cold water is circulated around the plate to control the temperature of the protein solution retained in the plate.

  WO 03/080900 describes a crystal growth system such as a protein crystal. The system has an array of wells or channels that define a substrate configured to contain a crystallization solution. Accompanying an array of wells or channels is a temperature controller for creating different temperatures throughout the array.

  Appropriate temperature control during protein crystallization assays can prevent the decomposition of valuable analytes and increase the reproducibility of experimental results. It has been evaluated that it can help discovery. However, proper temperature control of the assay performed in the parallel method has proved difficult to date.

  It is an object of the present invention to provide a method and apparatus for incubating an analyte, for example for protein crystallization.

(Description of the Invention)
The inventor appreciates that the known methods and apparatus have drawbacks. The present invention has been devised taking this evaluation into account. Thus, according to a first embodiment, there is provided a method of processing an analyte using a portable incubator device, an incubator device having a plurality of cavities configured to contain an analyte to be incubated, the method comprising: Putting analytes into individual cavities; an incubator device that can be operated to control the temperature of the analytes contained in the cavities independently of each other. Incubating; and, when the incubator device is moved, an incubator device configured to maintain the desired incubation conditions, independent of power supply and external devices of the incubator device, wherein the analyte is incubated Between the first position and the second It is moved to the location, consisting of.

  The incubator device's ability to maintain the desired incubation conditions, independent of power supply and external devices of the incubator device, will incubate the analyte, so that during the incubation, the incubation device will move from the first position to the first position. 2 position. That is, for example, this analyte is dispensed into multiple cavities at an automated dispensing station (ie, the first position) and then moved to the storage position (ie, the second position) while incubation is in progress. Where the incubation process is completed over time.

  The present invention is based on the identification of moving the position of the incubation device in certain situations where the ambient temperature is variable and jeopardizes the stability of the incubated analyte. For example, the analyte is susceptible to temperature fluctuations during movement, which can cause irreversible changes in the analyte and prevent accurate analysis. According to the present invention, this problem is solved by this incubation device that maintains the desired incubation conditions during the transfer.

  Furthermore, the incubation device functions to control the temperature of the analytes entering the plurality of cavities independently of each other during the incubation. For example, the analyte in the first cavity can be maintained at a first temperature, such as 4 ° C, and the analyte in the second cavity can be maintained at a second temperature, such as 35 ° C. This allows the two studies to be performed at different temperatures at the same time, thereby reducing the time that the study is performed on the analyte under investigation.

  That is, when the incubator device is being moved, it can be configured to maintain the desired analyte temperature despite changes in ambient temperature.

  Alternatively or additionally, the analyte in the plurality of cavities may include at least one biological and non-biological compound.

  Alternatively or additionally, the analyte in the plurality of cavities can include at least one of protein, DNA, RNA, and stem cells.

  Alternatively or additionally, if the analyte is exposed to harmful incubation conditions, the analyte is susceptible to irreversible changes, which is disadvantageous for subsequent analysis of the analyte.

  Alternatively or additionally, the analyte may comprise a compound that is susceptible to crystallisation when exposed to harmful incubation temperatures. Thus, this method can be applied to biological crystallization; non-biological crystallization; enzyme kinetic process; fermentation process; polymer science process; stem cell preservation; polymerase chain reaction (PCR); At least one part of such DNA-related processes may be formed.

  Alternatively or additionally, the incubator device can optionally be configured to heat the analyte in the plurality of cavities; and to cool the analyte in the plurality of cavities.

  Alternatively or in addition, the incubator device: heats the analytes in the plurality of cavities independently of each other; and cools or at least one of the analytes in the cavities independently of each other It can be configured as follows.

  Alternatively or additionally, the incubator device may be selectively configured to transfer heat from an analyte contained in at least one cavity; or to transfer heat to an analyte contained in at least one cavity. .

  Alternatively or in addition, the incubator apparatus may include a temperature controller that can be operated to control the temperature of the analyte in the plurality of cavities.

  The scope of the present invention should not be construed as limited to independent temperature control of analytes in only two cavities. Indeed, the temperature of the analyte in more than one cavity or groups of cavities can be controlled independently. Thus, for example, if there are five cavities or groups of cavities, the five reviews can be performed simultaneously with a corresponding reduction in the review period and user effort.

  Alternatively or additionally, the incubator apparatus can be configured to create at least one different temperature across the plurality of cavities.

  Alternatively or additionally, the incubator device can be configured to control the temperature of the analytes entering at least two groups of cavities independently of each other. That is, the incubator apparatus can be configured to maintain the first group of cavities at a first temperature and the second group of cavities at a second temperature, wherein the first temperature and the second The temperatures are different from each other.

  Alternatively or additionally, the temperature controller can be operated to create at least one temperature gradient across the plurality of cavities.

  Alternatively or additionally, the incubator apparatus can be configured such that the temperature controller can be operated to create at least two temperature gradients across the plurality of cavities, wherein the first temperature gradient is across the first group of cavities, and The second temperature gradient is across the second group of cavities, and the first and second temperature gradients are independently controlled.

  Alternatively or additionally, the temperature controller can be operated to change the temperature of the analyte in the plurality of cavities relative to the ambient temperature. Therefore, the temperature of the analyte may be higher or lower compared to the ambient temperature. That is, the temperature of the analyte may be between about 4 ° C and about 35 ° C. Thus, the term incubator as used in this specification is intended to include not only devices that heat the analyte, but also devices that cool the analyte.

  Alternatively or additionally, the plurality of cavities may include at least one well and channel. The cavities (ie wells or channels) may be of substantially the same shape, eg shape and / or size. Alternatively, the cavity may have a substantially different form. This cavity may be of known or standard form.

  Alternatively or additionally, the plurality of cavities can be arranged in a two-dimensional array, eg, a 5 × 6 array of wells in an incubator apparatus.

  Alternatively or additionally, the plurality of cavities can be arranged in the incubator apparatus as an array, eg, an array of channels.

  Alternatively or additionally, the incubator apparatus may include a solid state heating / cooling apparatus.

  Alternatively or additionally, the temperature controller may include at least one Peltier heat pump. The Peltier heat pump can be configured and operable to control the temperature of the analyte entering one of the at least two cavities.

    Alternatively or additionally, the temperature controller may include at least two Peltier heat pumps. Individual Peltier heat pumps can be configured and operable to control the temperature of the analyte in one of the at least two cavities. That is, each Peltier heat pump can be configured and operable to control the temperature of an analyte in one of the cavities.

  Alternatively or additionally, the incubator apparatus may include a plurality of temperature sensors that can be individually operated to sense individual temperatures of the analytes that have entered the plurality of cavities. That is, at least one of the plurality of temperature sensors may be a thermistor such as a thermistor adapted for RT.

  Alternatively or additionally, the temperature controller of the incubator device can be operated based on temperatures sensed by a plurality of temperature sensors.

  Alternatively or additionally, the temperature controller can be operated to control the temperature of the analyte in the plurality of cavities for each predetermined temperature.

  Alternatively or additionally, the incubator apparatus may include a proportional, integral and derivative (PID) module that can be operated to control the temperature of the analyte in the plurality of cavities.

  Alternatively or additionally, the incubator apparatus may include a power source that can be operated to provide power for independent operation of the incubator apparatus. That is, the power source may include a battery.

  Alternatively or additionally, the incubator apparatus may include a cooling device configured to dissipate heat from the plurality of cavities. That is, the cooling device may include at least one heat sink coupled in heat to at least one of the plurality of cavities. That is, the heat sink can be coupled to multiple cavities with respect to heat. That is, the heat sink can be connected with respect to heat to a plurality of linearly arranged cavities.

  Alternatively or additionally, the at least one heat sink may be adjacent to at least one of the plurality of cavities.

  Alternatively or additionally, the at least one heat sink may be located on the side of the cavity relative to the opening of the cavity where the analyte enters the cavity.

  Alternatively or additionally, the at least one heat sink may be located on the side of the cavity opposite the cavity opening into which the analyte enters the cavity. This configuration has the advantage of providing a space on the side of the cavity. For example, such a space can be used for additional cavities.

  Alternatively or additionally, at least one heat sink may be included in at least a portion of the case of the incubator apparatus. Thus, for example, the cooling device includes a heat sink adjacent to the cavity, the heat sink connecting with the case in terms of heat, and the case instead serves as a heat sink.

  Alternatively or additionally, the cooling device can be coupled in terms of heat to the heating / cooling device of the incubator device.

  Alternatively or additionally, the incubator device may further include an interface configured for communication between the incubator device and a computer, such as a personal computer (PC). That is, the incubator device may be configured to be programmed by a computer via a computer interface.

  Alternatively or additionally, the incubator device may further include at least one sealing element for sealing the analyte contained in the at least one cavity.

  Alternatively or additionally, the incubator apparatus may further include at least one light source configured to illuminate the analyte that has entered the plurality of cavities. That is, the incubator apparatus may include a plurality of light sources individually configured to illuminate an individual one of the plurality of cavities.

  Alternatively or additionally, the at least one light source may be configured to illuminate the analyte entering the plurality of cavities from the side of the cavity opposite the cavity opening into which the analyte enters. Therefore, if the cavity is open upward, at least one light source can be backlit against the cavity. Backlighting allows an optical inspection of the analyte that has entered the incubator device, for example a microscope inspection.

  Alternatively or additionally, the at least one light source may include a light emitting diode (LED).

  Alternatively or additionally, the incubator apparatus may be configured to change the brightness of at least one light source.

  Alternatively or additionally, the plurality of cavities may feature a receptacle that includes at least a portion of a material that allows light to pass therethrough.

  Alternatively or additionally, the incubator apparatus may feature a substantially rectangular footprint that rests on top of the ground in use.

  Alternatively or additionally, the incubator device may be robot handler compatible. For example, the incubator apparatus is of SBS format with a footprint of 85.48 mm ± 0.25 mm × 127.76 mm ± 0.25 mm or a Linbro plate format with a footprint of 150 mm × 108 mm × 22 mm. Also good.

  The incubator device may be an experimental device. That is, the experimental device may be configured for at least one chemical and biological application. Such an application is a feature of the experimental method. For example, the incubator device may be used for at least one of biological crystallization, enzyme kinetic processes, fermentation processes, polymer science processes, stem cell storage, polymerase chain reaction (PCR) and similar such DNA related processes. It may be configured for.

  Alternatively or additionally, the plurality of cavities can form an analyte containing member. That is, the analyte housing member may be removed from the incubator device.

  Alternatively or additionally, the analyte containing member may include a plurality of cavities with individual cavities including a plurality of wells.

  Alternatively or additionally, the analyte containing member may be of a known form. For example, the analyte containing member may be a microtiter plate.

  Alternatively or additionally, the analyte containing member may be formed of a plastic material.

  Alternatively or additionally, the analyte containing member may include a thermal insulation between the cavities.

  Alternatively or additionally, the analyte containing member may be a single member.

  Alternatively or additionally, the analyte containing member may comprise at least two container members, i.e. individual container members consisting of an individual one of at least two individual cavities. That is, when using an incubator apparatus, the incubator apparatus can be configured such that at least two container members are separated from each other. Accordingly, the cavities in the container member can be insulated from each other.

  Alternatively or additionally, the incubator device may be configured to be portable.

  Alternatively or additionally, the temperature in at least one of the cavities may be recorded. That is, the temperature may be recorded when the incubator device is moving from the first position to the second position.

  Alternatively or additionally, the recorded temperature may be at least one of: a temperature displayed to a user of the incubator device; a temperature at which communication was made to the device at the second location.

  Alternatively or additionally, the incubator device may be stored in the storage unit at at least one of the first and second positions, the storage unit being configured to support a plurality of incubator devices. There is also. That is, the storage unit, when used, may be configured to support multiple incubator devices to divide a substantially identical footprint that is above and away from the ground.

  According to a second embodiment of the present invention, a portable incubator device comprising a plurality of cavities is provided, each individually configured to contain an analyte to be incubated, wherein the incubator devices are: To control the temperature of the analyte entering the cavity of the device: and configured to move from the first position to the second position while the analyte is being incubated, and when moving the incubator device, Independent of the power supply and the external device of the incubator device, it is configured to maintain desirable incubation conditions.

  The second embodiment of the present invention may include one or more features of the first embodiment of the present invention.

  According to a third embodiment of the present invention, there is provided an incubator storage device comprising a storage unit according to the second embodiment of the present invention and a plurality of portable incubator devices, wherein the storage unit, when used, each of the plurality of incubator devices. Configured to support.

  That is, if an incubator storage device is used, the storage unit may be configured to support multiple incubator devices to divide a substantially identical footprint that is above and away from the ground.

  Additional aspects of the third embodiment of the invention may include one or more features of the first or second embodiment of the invention.

  According to a fourth embodiment of the present invention, there is provided a portable incubator device comprising a plurality of cavities individually configured to contain an analyte to be incubated, the incubator device comprising: a plurality of cavities The temperature of the entering analytes is controlled independently of each other; and is configured to move from the first position to the second position while the analytes are incubated; the incubator device further includes the analyte Included is at least one heat sink disposed on at least one side of the cavity opposite the opening of the receiving cavity.

  Aspects of the fourth embodiment of the present invention may include one or more features of the first to third embodiments of the present invention.

  According to a fifth embodiment of the present invention, there is provided an incubator storage device comprising a storage unit and a plurality of portable incubator devices, wherein the storage unit is configured to support each of the plurality of incubator devices when used. The portable incubator apparatus includes a plurality of cavities, each cavity configured to contain the analyte to incubate, the incubator apparatus: controlling the temperature of the analytes entering the plurality of cavities independently of each other And configured to move from the first position to the second position while the analyte is being incubated.

  Aspects of the fifth embodiment of the present invention may include one or more features of the first to fourth embodiments of the present invention.

  According to a further embodiment of the invention, an incubator device comprising a plurality of cavities is provided, wherein each cavity is configured to contain an analyte to be incubated, the incubator devices being independent of each other. It is configured to control the temperature of the analyte in the plurality of cavities.

  Aspects of further embodiments of the invention may include one or more features of the first to fifth embodiments of the invention.

(Individual explanation)
An incubator apparatus 10 according to the present invention is shown in FIG. The incubator device includes a main body 12 that holds an inlay 14 (constituting an analyte containing member) that is removable from the main body 12. The incubator apparatus is of the SBS format with a footprint of 85.48 mm ± 0.25 mm × 127.76 mm ± 0.25 mm that is adapted to be operated by a robotic high-throughput system. Accordingly, this footprint is consistent with the American National Standards Institute (ANSI) standard ANSI / SBS 1-2004. The incubator device 12 is provided with an electrical connector 16.

  The component parts of the incubator apparatus 10 are described in further detail herein with respect to the exploded view shown in FIG.

  The inlay 14 is characterized by a 5 × 6 two-dimensional array of wells 20 (constituting multiple cavities). Well locations are consistent with the ANSI / SBS 4-2004 standard for well locations relative to the microplate. The inlay 14 is made of a plastic material such as polycarbonate. Therefore, the plastic material provides thermal insulation between the inlay rows. The inlay 14 enters the incubator apparatus 10 through an opening formed in the upper part 22 of the same apparatus case. The incubator device 10 also includes a lower portion 24 of the device case. Both the upper and lower portions 22 and 24 provide an enclosure for the incubator apparatus 10. The upper and lower portions 22 and 24 of the case of this device are made of a chemically strong material such as nylon. Alternatively, the upper and lower portions 22 and 24 may function like a heat sink. In such a configuration, the top and bottom can be made of at least a portion of one or more materials commonly used to make heat sinks.

  In a form not shown in the inlay view, the inlay includes five separate inlay members, each inlay member being an array of wells in a row.

  The members inside the incubator apparatus 10 will be described. The printed circuit board 30 includes the following electric control circuit. The printed circuit board 30 is a conventional four-layer board having a thickness of 1 mm. Heat sinks 32 formed from copper or aluminum are physically attached to the printed circuit board in a conventional manner so that they make preferred temperature and electrical contact. The purpose of the heat sink 32 is to dissipate heat generated by heat pumps (described below) and electronic components. Further optional thermal management methods include forced cooling using an electric blower (not shown) according to conventional methods. The heat insulating material 34 is placed on the printed circuit board 30. The insulation is shaped to insulate the rows of wells 20 in the inlay 14 from each other and from the printed circuit board 30. The heat insulating material 34 is formed from polyurethane using 60% glass fiber up to UL94-V0 grade. A light emitting diode (LED) 36 is placed on the printed circuit board at a position corresponding to the well 20 of the inlay 14. The LED 36 is operated by an electrical circuit mounted on the printed circuit board 30 according to a well established design. The brightness and spectral composition of the LED 36 can be adapted to the demand for conventional automatic electronic coupling device (CCD) inspection instruments. A tray 38 attached to the insulation 34 features a 5 × 6 two-dimensional array of individual wells 20 configured to contain the wells of the inlay. A 5 × 6 two-dimensional array of wells in tray 38 is formed by five blocks, each block being arranged in one row and having one array of 6 wells. The tray 38 is formed from a metal having the desired thermal conductivity, such as aluminum or copper. Individual wells in tray 38 are individually LED 36 to illuminate analytes placed in wells 20 of inlay 14 by gaps in the individual well walls of the tray, taking into account, for example, the allowance of LED light paths. It is made to be able to emit light. Individual blocks of tray 38 are associated with two Peltier heat pumps placed on printed circuit board 30. The Peltier heat pump 40 is shown below in connection with FIG. A battery 42 is provided to enable portable operation. The apparent voltage is 3.7V and the capacity is 1000 mAh. A rechargeable battery such as Varta Easypack 1000 is used. The electric power for the incubator apparatus 10 can be supplied from an external power source (not shown) according to a conventional method. The status LED 44 operates to display the state of the incubator apparatus 10 when in use. The connector 46 enables serial communication (eg, RS485 or RS232) and parallel communication. Serial communication is used to program the temperature in the individual wells 20 of the inlay 14 and to output recorded temperature data. Parallel communication to the JTAG standard is used for programming the microcontroller on the printed circuit board 30 and for testing the firmware of the incubator device.

(First embodiment)
FIG. 3a shows the block 60 of the tray 38 of FIG. 2 in more detail and in accordance with the first embodiment. The block 60 includes a metal member 62 that features six individual spaced wells 64 for receiving the wells 20 of the inlay 14 in use. The two Peltier heat pumps 66 are arranged around the end of the metal member 62. A suitable heat pump is the Marlow Industries MI1011T with a body size of 6.6 mm x 6.6 mm, a maximum current of 1 A and a maximum voltage of 2V. The Peltier heat pump 66 is connected in series and is powered by a voltage source 68. The placement of the Peltier heat pump 66 at the individual ends of the inlay makes the temperature of the entire inlay uniform. The arrows in FIG. 3 indicate the direction of current flow. That is, the Peltier heat pump is operated by a Texas Instruments MOSFET H-bridge using a Texas Instruments DRV591. The output voltage level of the Texas Instruments DRV591 is controlled by a Texas Instruments DAC 7558 digital-to-analog converter, which in turn is controlled by a microcontroller device. Individual outputs from the Peltier heat pump driver are filtered by a passive LC filter to provide a DC driving voltage with less than 10% ripple. The design of the driver circuit for the Peltier heat pump is, for example, the main component, that is, the Peltier heat pump itself, Texas Instruments.
This is a sure method for those skilled in the art, including reference to standard text as described in the data sheets for DRV591 and the Texas Instruments DAC7558 digital-to-analog converter. A RT thermistor 70 is placed on the underside of the metal member 62 to provide an electrical resistance measured by the microcontroller device to determine temperature by table index according to a well-established method. The accuracy of the temperature measurement is more than 0.5 ° C. without having to calibrate the electrical circuit associated with the individual thermistor 70.

(Second Embodiment)
FIG. 3b shows the block 72 of the tray 38 of FIG. 2 according to the second embodiment. The components and functions of this embodiment shown in FIG. 3b are the same as for the first embodiment described for FIG. 3a, except as described below. Although the Peltier heat pump 66 is located on the opposite side of the metal member 62, the Peltier heat pump 66 is located directly below the metal member 62 (ie, on the side of the metal member 62 opposite to the opening of the well 64). The heat sink 74 is located directly below the Peltier heat pump 66 and is in contact therewith. As shown in FIG. 2, the heat sink 32 of the first embodiment is located on the side surface of the well 20. Thus, the arrangement of the second embodiment creates a space around the well that may be used, for example, to supply additional wells.

  The provisions of digital control of the Peltier heat pumps 40, 66 and digital display of the measured temperature in the well 20 of the inlay 14 allow closed circuit digital control by the microcontroller device. For this purpose, a proportional / integral / derivative control program is provided in the microcontroller. The proportional / integral / derivative control program is designed and functions according to conventional methods. Although not shown in the figure, the microcontroller placed on the printed circuit board is a Freescale 56F8123 hybrid digital signal processor (DSP) / microcontroller. The supporting electrical circuitry for the microprocessor is designed according to standard design methods such as those based on data sheets provided by the microprocessor manufacturer.

The firmware executed by the microprocessor is shown in the flowchart 80 of FIG. Firmware design follows conventional well-established methods. The firmware function shown in FIG. 4 will be obvious to a practically skilled reader taking into account the foregoing. In summary, the microprocessor firmware enables the following features:
-Incubator equipment setup, control and diagnostics.
-Communication via connector 16 connected to a personal computer (PC) (not shown).
-Remote control by PC.
-PID control.

  Under firmware control, the temperature measured by the thermistor 70 is stored, for example, in a solid state memory. If the device is moving from one position to another, temperature recording continues. Although not shown in the figure, the temperature can be indicated by an LED or LCD display according to well-known design methods. Such an indication is for the convenience of the user who may carry the device from one location to another, and therefore the user may affect any stability of the analyte. Analytical temperature can be monitored for dangerous temperature changes or levels. Alternatively or additionally, the recorded temperature can be communicated via the connector 16 to monitor the target elsewhere, for example to use the device in the moved position.

  The use of an incubator device for protein crystallization is illustrated in FIGS. 1 to 3 herein. The new inlay 14 is inserted into the incubator device 10 through an opening provided at the top of the device case 22 so that the inlay well 20 enters the well of the tray 38. Analytes, including protein, saline, detergents and other stabilizers, are dispensed into 20 wells of inlay 14. For example, to start an incubation period of one week to three months, the well 20 is sealed, for example with tape or oil, before the incubator operation is started according to the firmware program present in the microprocessor. The incubator may be started before the analyte enters the well 20. The equipment of the Peltier heat pump provided in each of the five blocks of the tray 38 makes it possible to independently control the temperature of the analyte contained in the well 20 entering the block. This means that the incubator device 10 may affect the analytes contained in the device for up to five different temperature regions within the incubation period. Although not shown, the two Peltier heat pumps 66 operate independently of each other to operate at different temperatures in the range of about 4 ° C. to about 35 ° C. Thus, a temperature gradient can be installed along the block between the two Peltier heat pumps 66. In an embodiment of Peltier heat pumps connected in series and independently controlled, closed circuit control by the thermistor 70 associated with the individual blocks of the tray 38 provides absolute accuracy of better than 0.5 ° C. Temperature control during the incubation period depends on the PID control function performed by the microprocessor. For example, the temperature within the individual blocks of the tray 38 can be maintained during the incubation period, or changes in temperature can be affected during the incubation period. During the incubation period, a user, such as a researcher, can periodically inspect the analytes that have entered the individual wells 20 under the microscope utilizing the backlighting emitted by the LED 36.

  It should be noted that the installation of the incubator device in the SBS format means that the robot handling device can be used for moving, filling, sealing and optical inspection of the device 10.

  FIG. 5 shows the incubator storage device 100. The incubator storage device 100 includes a storage unit 102 configured to support five incubator devices 10. The storage unit 102 includes a backplane 104 that extends vertically when the incubator storage device 100 is used. The shelf 106 extends horizontally from the backplane 104. Incubator apparatus 10 can be supported on individual shelves 106. The incubator storage device 100 enables space-efficient storage of the incubator device 10.

  Further features and advantages of the invention will become apparent from the following individual description by way of example only and with reference to the accompanying figures.

FIG. 1 is a perspective view of an incubator apparatus according to the present invention. FIG. 2 is an exploded view of the incubator apparatus of FIG. FIG. 3a is a diagram of two Peltier heat pumps used in the incubator apparatus of FIGS. 1 and 2 according to the first embodiment. FIG. 3b is a diagram of two Peltier heat pumps used in the incubator apparatus of FIGS. 1 and 2 according to a second embodiment. FIG. 4 is a flowchart showing the firmware operation during use of the incubator apparatus. FIG. 5 is a perspective view of an incubator storage device according to the present invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 Incubator apparatus 12 Main body 14 Inlay 16 Electrical connector 20 Well 22 Upper part of apparatus case 24 Lower part of apparatus case 30 Printed circuit board 32 Heat sink 34 Heat insulating material 36 LED
38 Tray 40 Peltier heat pump 42 Battery 44 Status LED
46 connector 60 block 62 metal member 64 well 66 Peltier heat pump 68 voltage source 70 thermistor 72 block 74 heat sink 100 incubator storage device 102 storage unit 104 backplane 106 shelf

Claims (62)

Placing the analyte in each of the cavities;
An incubator device operable to control the temperature of an analyte contained in the plurality of cavities independently of each other, incubating the analyte in the plurality of cavities; and the incubator device moving The incubator device configured to maintain desirable incubation conditions independent of power supply and external devices of the incubator device, wherein the first time while the analyte is incubated Moving the incubator device from a position to a second position;
A method comprising:
A method of processing said analyte using a portable incubator device, said incubator device having said plurality of cavities individually configured to contain said analyte to be incubated. The method of claim 1, wherein when the incubator device is being moved, the incubator device is configured to maintain a desired analyte temperature despite ambient temperature changes. The method of claim 1 or 2, wherein the analyte in the plurality of cavities comprises at least one biological and non-biological compound. The method according to claim 1, wherein the analyte contained in the plurality of cavities includes at least one of protein, DNA, RNA, and stem cells. 5. The analyte according to any one of claims 1 to 4, wherein the analyte is susceptible to irreversible changes when the analyte is exposed to harmful incubation conditions, which is disadvantageous for subsequent analysis of the analyte. the method of. 6. A method according to any one of the preceding claims, wherein the analyte comprises a compound that is susceptible to crystallisation when exposed to harmful incubation temperatures. The incubator device is selectively configured to heat an analyte contained in the plurality of cavities; and to cool the analyte contained in the plurality of cavities. The method described in one. The incubator device: heating the analytes in the plurality of cavities independently of each other; and cooling the analytes in the plurality of cavities independently of each other or at least one of them 8. The method according to any one of claims 1 to 7, wherein the method is configured. 9. The incubator device is configured to selectively: transfer heat from an analyte in at least one cavity; and transfer heat to an analyte in at least one cavity. The method as described in any one of these.   10. A method according to any one of the preceding claims, wherein the incubator device comprises a temperature controller operable to control the temperature of an analyte entering the plurality of cavities.   11. A method according to any one of the preceding claims, wherein the incubator device is configured to create at least one temperature difference that varies across the plurality of cavities.   12. A method according to any one of the preceding claims, wherein the incubator device is configured to control the temperature of analytes entering at least two groups of cavities independently of each other.   The incubator device can be configured to maintain a first group of cavities at a first temperature and a second cavity at a second temperature, wherein the first temperature and the second temperature are The method of claim 12, which is different.   14. The method according to any one of claims 1 to 13, wherein the plurality of cavities include at least one well and channel.   15. A method according to any one of the preceding claims, wherein the cavities are of substantially the same form.   15. A method according to any one of the preceding claims, wherein the cavities may be in substantially different forms. 17. A method according to any one of claims 1 to 16, wherein the plurality of cavities are disposed in the incubator device in a two-dimensional array.   18. A method according to any one of the preceding claims, wherein the incubator device comprises a solid state heating / cooling device.   19. A method according to any one of the preceding claims, wherein the incubator device comprises at least two Peltier heat pumps.   20. The method of claim 19, wherein an individual Peltier heat pump is configured and operable to control the temperature of the analyte that enters at least one of the plurality of cavities.   21. The incubator apparatus according to any one of claims 1 to 20, wherein the incubator device comprises a plurality of temperature sensors that can be individually operated to sense individual temperatures of analytes in one of the plurality of cavities. Method.   The method of claim 21, wherein at least one of the plurality of temperature sensors is a thermistor.   23. A method according to claim 21 or 22, wherein a temperature controller of the incubator device operates depending on the temperature sensed by the plurality of temperature sensors.   24. A method according to any one of claims 21 to 23, wherein the temperature controller is operable to control the temperature of the analyte entering the plurality of cavities for each predetermined temperature.   25. A method according to any of claims 1 to 24, wherein the incubator device further comprises a proportional-integral-derivative (PID) module operable to control the temperature of an analyte entering the plurality of cavities.   26. A method according to any one of the preceding claims, wherein the incubator device comprises a power source operable to supply power for independent operation of the incubator device.   27. The method of claim 26, wherein the power source includes a battery.   28. A method according to any one of the preceding claims, wherein the incubator device comprises a cooling device configured to dissipate heat from the plurality of cavities.   30. The method of claim 28, wherein the cooling device includes at least one heat sink coupled in heat to at least one of the plurality of cavities.   30. The method of claim 29, wherein the heat sink is coupled to the plurality of cavities with respect to heat.   31. The method of claim 30, wherein the heat sink is thermally coupled to a plurality of linearly arranged cavities.   32. A method according to any one of claims 29 to 31, wherein at least one heat sink is adjacent to at least one of the plurality of cavities.   33. A method according to any one of claims 29 to 32, wherein at least one of the heat sinks is located on a side of the cavity with respect to the opening of the cavity where the analyte enters the cavity.   33. A method according to any one of claims 29 or 32, wherein at least one of the heat sinks may be disposed on a side of the cavity opposite the opening of the cavity where the analyte enters the cavity. .   35. A method as claimed in any one of claims 28 to 34, wherein the cooling device is coupled with heat to a heating / cooling device of the incubator device.   36. The method of any one of claims 1-35, wherein the incubator device further comprises an interface configured for communication between the incubator device and a computer.   38. The method of claim 36, wherein the incubator device is configured to be programmed by a computer via an interface.   38. A method according to any one of the preceding claims, wherein the incubator device comprises a sealing element for sealing an analyte contained in at least one cavity.   39. The method of any one of claims 1-38, wherein the incubator device includes at least one light source configured to illuminate an analyte that has entered the plurality of cavities.   40. The method of claim 39, wherein the incubator apparatus includes a plurality of light sources individually configured to illuminate an individual one of the plurality of cavities.   41. A method according to claim 39 or 40, wherein the analyte is configured to illuminate an analyte entering a plurality of cavities from a side of the cavity opposite the mouth of the cavity into which it entered.   42. A method according to any one of claims 39 to 41, wherein the at least one light source comprises a light emitting diode (LED).   43. A method according to any one of claims 39 to 42, wherein the incubator device is configured to change the brightness of the at least one light source.   44. A method according to any one of claims 1 to 43, wherein the plurality of cavities are characterized by a receptacle including at least a portion of a substance that allows light to pass through.   45. A method according to any one of the preceding claims, wherein the incubator device has a substantially rectangular footprint that rests on the ground away from the ground in use.   46. A method as claimed in any one of the preceding claims, wherein the incubator device is robot handler compatible.   47. The method of claim 46, wherein the incubator device is moved from a first position to a second position by a robot handler.   48. A method according to any one of claims 1-47, wherein the incubator device is a laboratory device.   49. The method of any one of claims 1-48, wherein the plurality of cavities are configured in an analyte containing member.   50. The method of claim 49, wherein the analyte containing member can be removed from the incubator device.   51. The method of claim 49 or 50, wherein the analyte containing member comprises a plurality of cavities with individual cavities comprising a plurality of wells.   52. A method according to any one of claims 49 to 51, wherein the analyte containing member is made of plastic.   53. A method according to any one of claims 49 to 52, wherein the analyte containing member comprises a thermal insulation between the plurality of cavities.   54. A method according to any one of claims 49 to 53, wherein the analyte containing member is a single member.   55. A method according to any one of claims 1 to 54, wherein the incubator device is configured for portable use.   56. A method according to any one of claims 1 to 55, wherein the temperature in at least one of the plurality of cavities is recorded.   57. The method of claim 56, wherein the temperature is recorded as the incubator device is moving from a first position to a second position.   58. The recorded temperature is at least one of: a temperature displayed to a user of the incubator device; a temperature at which communication was made to the device at the second location. the method of.   The incubator apparatus is stored in a storage unit at at least one of a first position and a second position, and the storage unit is configured to support a plurality of incubator apparatuses. 58. The method according to any one of -58.   60. The method of claim 59, wherein the storage unit is configured to support the plurality of incubator devices to substantially divide the same footprint that is above and away from the ground in use. A portable incubator device comprising a plurality of cavities individually configured to contain the analyte to be incubated;
Configured to control the temperature of analytes contained in the plurality of cavities independently of each other; and configured to be moved from a first position to a second position while the analytes are incubated;
An incubator apparatus configured to maintain desirable incubation conditions independent of power supply and external devices of the incubator apparatus when the incubator apparatus is being moved.   62. An incubator storage device comprising a storage unit and a plurality of portable incubator devices according to claim 61, wherein the storage unit is configured to individually support the plurality of incubator devices when used.

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